Paired donor exchange systems to avoid blood type incompatibility problems can work for liver transplants as they have for kidneys, researchers said.

Action Points

Explain to interested patients that transplants involving donors and recipients with mismatched blood types can have poorer outcomes and are generally avoided if possible.

Explain that this problem can be avoided in living donor transplants by matching willing donors with compatible recipients in "donor exchanges." In such arrangement, a patient's friend or relative who had volunteered to donate an organ actually gives it to another patient, whose own friend or relative in turn donates an organ to the first patient.

Explain that these studies showed that donor exchanges can work for liver transplants as well as for kidney transplants, where they were pioneered.

Paired donor exchange systems designed to avoid blood type incompatibility problems can work for liver transplants as well as for kidneys, researchers said.

A program at Asan Medical Center in Seoul, Korea, in 2003 has performed 16 donor exchanges to allow recipients to receive ABO-identical or compatible liver lobes, Sung-Gyu Lee, MD, and colleagues reported in the April issue of Liver Transplantation.

The same journal carried a report from Hong Kong surgeons who arranged a paired donor interchange for liver transplant in which one of the recipients needed urgent transplantation.

Lee and colleagues in Seoul wrote that their experience demonstrates that exchange programs are "a feasible modality for overcoming donor ABO incompatibility."

Living donor liver transplants have become increasingly popular and are now the dominant mode of liver transplant in some parts of the world, especially in Asia, where deceased donor transplants are unpopular.

In many cases, however, volunteer donors have a blood type incompatible with the recipient. ABO-incompatible transplants are performed when there is no other choice, but outcomes are generally poorer.

Donor-recipient incompatibility is also a problem for kidney donations. To overcome it, donor exchange systems for kidneys were set up in the 1980s to match donor-recipient pairs with others who have the opposite incompatibility.

Thus, a pair in which the prospective donor is type A and the recipient is type B could be linked to another pair whose donor is type B and recipient is type A.

The first donor's organ goes to the second recipient, while the first recipient receives an organ from the second donor. The surgeries can be performed simultaneously or in sequence.

More than two ABO-incompatible donor-recipient pairs may be matched to facilitate transplants. One chain involving at least 10 kidney transplants over eight months, at six transplant centers in five states, was reported last year, for example.

The success of such programs for kidney transplants has spurred interest in similar arrangements for living donor liver transplants.

Lee and colleagues reported on their experience from 2003 to 2009 with 16 adult donor exchanges, featuring six types of blood type incompatibility. One procedure involved a dual graft, hence there were 17 donors involved.

All living donor liver transplants in Korea must be approved by the local equivalent of the United Network for Organ Sharing (UNOS), the group that oversees organ transplantation in the U.S.

Because there was no relationship between the donors and recipients in these exchanges, special permission from the organization was required in each case, Lee and colleagues explained.

In all cases, the donor-recipient pairs participating in the exchange underwent surgery simultaneously.

Lee and colleagues required the simultaneous surgeries "to prevent cancellation of a donation due to later conflict or emotional change," a risk with sequential procedures.

Twelve of the surgeries were scheduled ahead of time, while four were performed on an emergency basis.

Three of the latter were classed as having acute-on-chronic liver failure, with a UNOS status of 2a, while the fourth showed rapid deterioration in Model for End-Stage Liver Disease scores shortly after agreeing to a donor swap.

Outcomes appeared to be similar to those expected from ABO-compatible transplants. All donors recovered successfully, Lee and colleagues reported. Among recipients, five-year survival rates for both grafts and patients were 93.8%.

One patient died after 54 days from graft failure associated with active hepatitis C virus replication. Another patient suffered chronic rejection and received a second transplant from a deceased donor at 65 months.

The other report in Liver Transplantation, from Chung Mau Lo, MD, and colleagues at Queen Mary Hospital in Hong Kong, described how they put together a donor exchange for a patient suffering liver failure from an acute hepatitis B virus (HBV) flare.

The patient had blood type A. Several relatives with type A offered to serve as liver donors, but they all tested positive for HBV. However, an HBV-free sister-in-law with blood type B also volunteered.

Because of the incompatibility, Lo and colleagues suggested a donor swap with another patient on a transplant waiting list. That patient had blood type B, but his type A wife had volunteered to be a liver donor, and the medical team had already discussed with them the possibility of a paired exchange.

The outcomes were somewhat bumpy. The recipient already on the waiting list had experienced previous bouts with bacterial peritonitis, which produced severe adhesions in his abdomen that were revealed when the surgeons opened it up for the transplant and made his transplant more challenging.

As a result, Lo and colleagues reported that the necessary dissection was "tedious" and caused "much bleeding," but was successful enough to allow the transplant to proceed with an uneventful recovery.

The other recipient also recovered well, but the donor in that case -- the sister-in-law of the HBV patient -- had a difficult postoperative experience. Her liver function became impaired and doctors discovered an accumulation of peritoneal fluid.

They suspected biliary leakage but could not find a specific site. Biopsy of her liver remnant showed 60% vacuolization, Lo and colleagues reported, with infiltration of eosinophils.

In response to deteriorating liver and kidney function and signs of systemic inflammation, with no identifiable cause, she was treated with intravenous immunoglobulin and hydrocortisone. She then recovered and was finally discharged from the hospital after 24 days.

Ten months after transplant, both recipients and both donors were in good health with normal liver function.

Lo and colleagues noted that the ethics of such exchanges can be complicated. Donors are motivated by their desire to save the life of the related patient, but a complete stranger will be the one to receive their donated organ.

So while the donor exchange "should not overshadow the primary intention of the donor," they wrote, "once the operations are started, the survival of one recipient should not be compromised by the other."

This concern became immediate in the case of the recipient with the abdominal adhesions, which very nearly rendered his transplant impossible.

If that had happened, his wife would have had to continue with her donation to the other recipient, without having saved her husband.

Lo and colleagues suggested that donor exchanges should be performed only in small-scale clinical trials under close supervision "to ensure the safety and physical and psychological well-being of the donors."

In an accompanying editorial, two surgeons at Johns Hopkins University in Baltimore -- which pioneered living donor exchanges -- agreed that they involve serious ethical as well as logistical hurdles.

These appear to be more significant for liver versus kidney transplants because the surgeries are more complicated for both donors and recipients, limiting the number of patients for whom these exchanges will prove feasible, Dorry Segev, MD, and Robert A. Montgomery, MD, noted.

Nevertheless, they wrote, "Those patients who find matches through liver paired donation obviously benefit significantly from the availability of this modality and from the innovative thinking of transplant providers," including the authors of these reports.

"We commend their success and hope that further efforts will be made to disseminate this modality internationally and to identify and expand the patient population that stands to benefit from it," the editorialists wrote.

No external funding was received for either report.

The authors and editorialists reported no potential conflicts of interest.

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